The present invention relates to novel (3-amino-1-propynyl)pyrrolidine compounds, pharmaceutical compositions containing the compounds and to the use of the compounds for the treatment of central cholinergic disfunction.
Senile Dementia of the Alzheimer's Type (SDAT) is a neurodegenerative disease which results in the progressive impairment of memory. Post-mortem autopsies of brain tissue from SDAT patients have shown a marked decrease in cholinergic neurons. Taken together these observations form the basis for the cholinergic hypothesis for memory loss. A series of chemical synthesis projects have been initiated in the geriatric program to discover selective cholinergic agonists to ameliorate the symptons of this degenerative disease.
In this respect, a number of derivatives of the cholinergic agent, oxotremorine, have been synthesized. Resul, B. and coworkers, Eur. J. Med. Chem., 1982, 17, 317 report the synthesis of N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide, referred to as BM-5, which acts as an antagonist at some muscarinic sites while being an agonist at most others. It has been suggested that this type of compound may be useful for the therapy of Alzheimer-type dementia. Lundkvist, J.R.M., et al., J. Med. Chem., 1989, 32, 863-869 synthesized a series of conformationally restricted analogues of BM-5 which differ structurally from those of the present invention.